Cheng I K, Ho S K, Chan D T, Ng W K, Chan K W
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam.
Am J Kidney Dis. 1996 Aug;28(2):283-8. doi: 10.1016/s0272-6386(96)90315-7.
Nodular glomerulosclerosis secondary to deposition of monoclonal immunoglobulin (Ig) light chains with or without heavy chains is a recognized clinicopathological entity. Recent reports have demonstrated that an identical glomerular lesion may also occur as a result of truncated tau Ig heavy chain deposition. We investigated the nature of Ig deposits in a patient who presented with rapidly progressive renal failure secondary to crescentic nodular glomerulosclerosis. This patient had a relapsing clinical course responsive to treatment with steroid and cyclophosphamide therapy. In this case, both the glomeruli and tubular basement membrane contained granular immune deposits that were reactive to polyclonal antibodies against alpha but not tau or mu Ig heavy chains and nonreactive to anti-kappa and anti-lambda light chain reagents. A monoclonal population of plasma cells secreting alpha and kappa chains was present in the patient's marrow despite the finding of a normal percentage of plasma cells. Serum Immunoelectrophoresis was normal, but immunofixation demonstrated the presence of a monoclonal alpha/kappa band. Immunoblot under dissociating and nondissociating conditions showed that both the patient's urine and serum contained Ig fragments that comprised dimer or monomer of an abnormally short alpha Ig heavy chain (approximately 26 kd) with or without associated kappa light chain. The identity of the abnormal serum alpha Ig heavy chain with that of the glomerular Ig deposits was supported by the finding that both were nonreactive against alpha 1 and alpha 2 subclass-specific monoclonal antibodies despite their reactivity to polyclonal antibodies. Because these monoclonal antibodies would react with structural determinants, which differ between alpha 1 and alpha 2 Ig heavy chains but not those common between them, and because the differences in amino acid sequence between the two largely lie in the CH1 and CH2 domains of the alpha Ig heavy chain, it is hypothesized that the abnormally short alpha Ig heavy chain produced by plasma cells in this patient contains deleted CH1 and CH2 domains similar to the findings in patients with tau Ig heavy chain deposition disease.
继发于单克隆免疫球蛋白（Ig）轻链沉积（伴或不伴重链沉积）的结节性肾小球硬化是一种公认的临床病理实体。最近的报告表明，相同的肾小球病变也可能由于截短的tau Ig重链沉积而发生。我们研究了一名因新月体结节性肾小球硬化继发快速进行性肾衰竭患者的Ig沉积物的性质。该患者有复发的临床病程，对类固醇和环磷酰胺治疗有反应。在这个病例中，肾小球和肾小管基底膜都含有颗粒状免疫沉积物，这些沉积物对针对α但不对tau或μ Ig重链的多克隆抗体有反应，而对抗κ和抗λ轻链试剂无反应。尽管患者骨髓中浆细胞百分比正常，但存在分泌α和κ链的单克隆浆细胞群。血清免疫电泳正常，但免疫固定显示存在单克隆α/κ条带。在解离和非解离条件下的免疫印迹显示，患者的尿液和血清中都含有Ig片段，这些片段由异常短的α Ig重链（约26kd）的二聚体或单体组成，伴或不伴有相关的κ轻链。异常血清α Ig重链与肾小球Ig沉积物的一致性得到了以下发现的支持：尽管它们对多克隆抗体有反应，但两者对α1和α2亚类特异性单克隆抗体均无反应。因为这些单克隆抗体将与α1和α2 Ig重链之间不同但它们之间共有的结构决定簇发生反应，并且因为两者之间的氨基酸序列差异主要位于α Ig重链的CH1和CH2结构域，所以推测该患者浆细胞产生的异常短的α Ig重链含有与tau Ig重链沉积病患者相似的缺失的CH1和CH2结构域。
